Predictors of treatment response to semaglutide for weight management

Abstract

The emergence of weekly, injectable glucagon-like peptide-1 (GLP-1) receptor agonists has revolutionized the obesity management landscape. Numerous studies have shown high efficacy as well as great variability in weight loss, highlighting the need for this mini review, summarizing current evidence about predictors of semaglutide-related weight loss. The first well-known determinant of semaglutide-induced weight loss is the presence of type 2 DM which is associated with significantly lower body weight reduction. The second predictor is sex, with females exhibiting a greater weight loss than males by a mean 6%. In addition, higher maintenance dose of 7.2 mg is superior to standard 2.4 mg dose in weight reduction by a mean 3%. There is no clear association of age and baseline body mass index with the magnitude of semaglutide-driven weight loss, except for the possibility of adolescence enhancing and overweight reducing this treatment effect. The potential impact of genetic polymorphisms of individual treatment response to semaglutide remains incompletely understood, limited so far to a modest effect of specific variants in GLP1 receptor gene. Another potential predictor of response could be obesity phenotype, with preliminary data supporting greater effectiveness of semaglutide in individuals with ‘‘hungry gut’’ phenotype. Type of lifestyle modification does not seem to have a significant effect on the variability of semaglutide-driven weight loss. Further studies are needed to expand knowledge about predictors of response to semaglutide, paving the way for validated predictive models in order to guide clinical decision-making and provision of personalized obesity care.